This invention relates to indwelling intravascular medical devices with improved compatibility with the intravascular environment. It particularly relates to intravascular prosthetic devices such as vascular grafts, vascular patches, or stents used to repair injured or defective blood vessels.
Medical devices which serve as indwelling intravascular devices such as vascular prostheses, catheters and the like are well known. However, the use of such biomaterials in medical devices can stimulate adverse body responses, including rapid thrombogenic action and inflammatory tissue reactions. Thus, both blood and tissue can be affected by the presence of such materials. For blood compatibility, it is well known that various plasma proteins play a role in initiating platelet and fibrin deposition on device surfaces. However, there is no single theory which explains why one material will prove to be exceptionally compatible with blood while another is not. A protein can adsorb to different material surfaces by different methods due to the wide variety of functional groups on the exterior of all proteins. Notwithstanding the lack of a theoretical basis to predict blood compatibility, tests have shown that some materials are particularly susceptible to thrombosis while other materials have been found to be exceptionally compatible with blood in intravascular applications.
Similarly, tissue reactions with medical devices are known to be important but are not well understood. The capacity of the natural endothelial cell lining of a blood vessel to regenerate, resist thrombosis and to resist bacterial invasion is well known. It is therefore desirable when using indwelling intravascular medical devices to maintain the existing endothelial cell layer and to extend the endothelial cell layer to cover the blood-contacting portion of the device surface. The response of the body to vascular graft materials, for example, can be to form a pseudointima, a surface lining of fibrin and entrapped blood-born cells on the graft; or to form a neointima, an endothelial cell monolayer covering the graft with or without the presence of an underlying structure of fibroblasts or smooth muscle cells. One adverse consequence of neointimal growth can be the development of neointimal fibrous hyperplasia, exuberant tissue growth within the neointima or within the natural vessel tissue at the anastomosis which can threaten blood vessel closure (especially in small blood vessels such as those having a diameter of only 3-4 mm). It is therefore desired that such hyperplasia be suppressed following the implantation of a medical device.
Materials to be used in vascular prostheses such as vascular grafts, vascular patches and stents are therefore particularly demanding in terms of blood compatibility and tissue compatibility since they are intended to be permanently affixed in the blood vessel and since they are typically applied at the site of a blood vessel injury that would be expected to trigger thrombosis and rapid cell growth as a normal part of the body's healing mechanism.
A "biomaterial" may be defined as a material that is substantially insoluble in body fluids and that is designed and constructed to be placed in or onto the body or to contact fluid of the body. Ideally, a biomaterial will not induce undesirable reactions in the body such as blood clotting, tissue death, tumor formation, allergic reaction, foreign body reaction (rejection) or inflammatory reaction; will have the physical properties such as strength, elasticity, permeability and flexibility required to function for the intended purpose; can be purified, fabricated and sterilized easily; will substantially maintain its physical properties and function during the time that it remains implanted in or in contact with the body.
An extensive program of testing was conducted for candidate polymeric biomaterials to determine their suitability for use in indwelling intravascular applications such as in vascular prostheses. In those tests, a stent was covered on only one side with a candidate polymer. The stent was then delivered on a balloon transluminally into a coronary blood vessel of a live pig having a diameter of approximately 3-4 mm where the stent was expanded to bring the candidate material into contact with the blood vessel to an extent similar to what may occur in a conventional percutaneous transluminal coronary angioplasty (PTCA) procedure. After a predetermined interval, the blood vessel containing the test stent was sectioned and the portion of the vessel in contact with the polymeric material was visually compared to the portion of the blood vessel that received no contact in order to determine the response of the blood vessel to the polymeric material. To date, few, if any, polymers have been found to be promising for small vessel intravascular applications due to adverse reactions with blood and/or the vascular tissue.
One approach to improved biocompatibility for biomaterials in particular applications is to modify only the surface of the biomaterial so that the bulk properties of the biomaterial are preserved while the surface characteristics are changed to provide a more favorable biological response from the body of the person in which it is implanted. One way to do this is to attach various "biomolecules" which can promote the attachment and growth of a normal cell layer such that the body accepts the cell-attached device as a normal part of the body. Biomolecules such as growth factors and cell attachment proteins which have been attached to the device surface could be used for this purpose. In addition, biomolecules such as antithrombogenics, antiplatelets, anti-inflammatories and the like have also been used to improve the biocompatibility of surfaces.
An example of another material modification approach can be found in U.S. Pat. No. 4,718,905 issued to Freeman in which the haptic loop elements of an intraocular lens are treated with ion beam implantation methods (preferably introducing nitrogen into the polypropylene material of the haptic loops) to make the loops more resistant to degradation by body fluids over time.
It is therefore an object of the present invention to provide an indwelling intravascular device which has a tissue-contacting and blood-contacting surface of improved biocompatibility.
It is also an object of the present invention to provide such an improved indwelling intravascular device in which the bulk properties of the base biomaterial are substantially unaffected.
It is yet another object of the present invention to provide a method for making such an improved indwelling intravascular device.